Induction of Functional Mesenchymal Stem Cells from Rabbit Embryonic Stem Cells by Exposure to Severe Hypoxic Conditions
Embryonic stem cells (ESCs) have the potential to be used as an unlimited cell source for cell transplantation therapy, as well as for studying mechanisms of disease and early mammalian development. However, applications involving ESCs have been limited by the lack of reliable differentiation method...
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doaj-bff2f8b73a084e8cbc30497082db09e82020-11-25T03:17:12ZengSAGE PublishingCell Transplantation0963-68971555-38922013-02-012210.3727/096368912X653291Induction of Functional Mesenchymal Stem Cells from Rabbit Embryonic Stem Cells by Exposure to Severe Hypoxic ConditionsTakeshi Teramura0Yuta Onodera1Toshiyuki Takehara2John Frampton3Toshiki Matsuoka4Syunsuke Ito5Koichi Nakagawa6Yoshihisa Miki7Yoshihiko Hosoi8Chiaki Hamanishi9Kanji Fukuda10Institute of Advanced Clinical Medicine, Kinki University Faculty of Medicine, Osaka, JapanInstitute of Advanced Clinical Medicine, Kinki University Faculty of Medicine, Osaka, JapanInstitute of Advanced Clinical Medicine, Kinki University Faculty of Medicine, Osaka, JapanDepartment of Biomedical Engineering, University of Michigan, Michigan, USADepartment of Biomedical Engineering, University of Michigan, Michigan, USACenter for Developmental Biology, Riken, Kobe, JapanDepartment of Orthopaedic Surgery, Kinki University Faculty of Medicine, Osaka, JapanDepartment of Orthopaedic Surgery, Kinki University Faculty of Medicine, Osaka, JapanDepartment of Biology-Oriented Science and Technology, Kinki University, Wakayama, JapanDepartment of Orthopaedic Surgery, Kinki University Faculty of Medicine, Osaka, JapanDepartment of Orthopaedic Surgery, Kinki University Faculty of Medicine, Osaka, JapanEmbryonic stem cells (ESCs) have the potential to be used as an unlimited cell source for cell transplantation therapy, as well as for studying mechanisms of disease and early mammalian development. However, applications involving ESCs have been limited by the lack of reliable differentiation methods in many cases. Mesenchymal stem cells (MSCs) have also emerged as a promising cell source, but as suggested in recent studies, these cells display limited potential for proliferation and differentiation, thereby limiting their usefulness in the clinic and in the laboratory. Unfortunately, effective methods for induction of MSCs from pluripotent stem cells have not been established, and the development of such methods remains a major challenge facing stem cell biologists. Oxygen concentration is one of the most important factors regulating tissue development. It has profound effects on cell metabolism and physiology and can strongly influence stem cell fate. Here we demonstrate that severe low O 2 concentrations (1%) can function as a selective pressure for removing undifferentiated pluripotent cells during the induction of MSCs from rabbit ESCs (rESCs) and that MSCs induced under severe hypoxic conditions function as normal MSCs; that is, they repopulate after cloning, express specific markers (vimentin, CD29, CD90, CD105, and CD140a) and differentiate into adipocytes, osteoblasts, and chondrocytes. Furthermore, we demonstrate that these cells can contribute to cartilage regeneration in an in vivo rabbit model for joint cartilage injury. These results support the notion that exposing ESCs to severe hypoxic conditions during differentiation can be used as a strategy for the preparation of functional MSCs from ESCs.https://doi.org/10.3727/096368912X653291 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takeshi Teramura Yuta Onodera Toshiyuki Takehara John Frampton Toshiki Matsuoka Syunsuke Ito Koichi Nakagawa Yoshihisa Miki Yoshihiko Hosoi Chiaki Hamanishi Kanji Fukuda |
spellingShingle |
Takeshi Teramura Yuta Onodera Toshiyuki Takehara John Frampton Toshiki Matsuoka Syunsuke Ito Koichi Nakagawa Yoshihisa Miki Yoshihiko Hosoi Chiaki Hamanishi Kanji Fukuda Induction of Functional Mesenchymal Stem Cells from Rabbit Embryonic Stem Cells by Exposure to Severe Hypoxic Conditions Cell Transplantation |
author_facet |
Takeshi Teramura Yuta Onodera Toshiyuki Takehara John Frampton Toshiki Matsuoka Syunsuke Ito Koichi Nakagawa Yoshihisa Miki Yoshihiko Hosoi Chiaki Hamanishi Kanji Fukuda |
author_sort |
Takeshi Teramura |
title |
Induction of Functional Mesenchymal Stem Cells from Rabbit Embryonic Stem Cells by Exposure to Severe Hypoxic Conditions |
title_short |
Induction of Functional Mesenchymal Stem Cells from Rabbit Embryonic Stem Cells by Exposure to Severe Hypoxic Conditions |
title_full |
Induction of Functional Mesenchymal Stem Cells from Rabbit Embryonic Stem Cells by Exposure to Severe Hypoxic Conditions |
title_fullStr |
Induction of Functional Mesenchymal Stem Cells from Rabbit Embryonic Stem Cells by Exposure to Severe Hypoxic Conditions |
title_full_unstemmed |
Induction of Functional Mesenchymal Stem Cells from Rabbit Embryonic Stem Cells by Exposure to Severe Hypoxic Conditions |
title_sort |
induction of functional mesenchymal stem cells from rabbit embryonic stem cells by exposure to severe hypoxic conditions |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2013-02-01 |
description |
Embryonic stem cells (ESCs) have the potential to be used as an unlimited cell source for cell transplantation therapy, as well as for studying mechanisms of disease and early mammalian development. However, applications involving ESCs have been limited by the lack of reliable differentiation methods in many cases. Mesenchymal stem cells (MSCs) have also emerged as a promising cell source, but as suggested in recent studies, these cells display limited potential for proliferation and differentiation, thereby limiting their usefulness in the clinic and in the laboratory. Unfortunately, effective methods for induction of MSCs from pluripotent stem cells have not been established, and the development of such methods remains a major challenge facing stem cell biologists. Oxygen concentration is one of the most important factors regulating tissue development. It has profound effects on cell metabolism and physiology and can strongly influence stem cell fate. Here we demonstrate that severe low O 2 concentrations (1%) can function as a selective pressure for removing undifferentiated pluripotent cells during the induction of MSCs from rabbit ESCs (rESCs) and that MSCs induced under severe hypoxic conditions function as normal MSCs; that is, they repopulate after cloning, express specific markers (vimentin, CD29, CD90, CD105, and CD140a) and differentiate into adipocytes, osteoblasts, and chondrocytes. Furthermore, we demonstrate that these cells can contribute to cartilage regeneration in an in vivo rabbit model for joint cartilage injury. These results support the notion that exposing ESCs to severe hypoxic conditions during differentiation can be used as a strategy for the preparation of functional MSCs from ESCs. |
url |
https://doi.org/10.3727/096368912X653291 |
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